Month: June 2021

Qualification of System and equipment’s in Pharmaceutical

What is Qualification :

The act of planning, carrying out and recording the results of tests on equipment’s and system to confirm its capabilities and to demonstrate that it will perform consistently as intended use and against predefined specification.

General requirements :

premises, systems, utilities and equipment should be appropriately designed, installed, qualified, operated, cleaned and
maintained, to suit their intended purpose.

Quality management systems should be in place to ensure that these remain in a qualified state throughout their life-cycle and Products should be produced and controlled using qualified equipment and instruments.

Qualification is applicable but are not limited to: certain rooms; water purification systems; cleaning systems; heating, ventilation and air-conditioning systems; compressed air systems; gas systems; and steam systems; as well as production equipment and analytical instruments.

The validation master plan, or other relevant document, should specify the policy, organization, planning, scope and stages applied in qualification on site, and should cover, for example, production, quality control and engineering.

Principles of quality risk management should be applied in qualification which include:

i A clear understanding of the system and the role it plays in establishing/protecting the process and quality, and all of the
potential ways (risks) the process or quality could be impacted by failures, events, errors, or time/use-based factors (deterioration, out of-tolerance instruments, wear and tear, and so on);

¡¡ defining all of the design, procedural and/or quality system controls required to protect against these potential risks. These controls either mitigate/reduce the risks and/or detect the impact to quality or process, should the risk occur (to ensure the failureh does not impact final product quality);
iii compiling evidence during the design, engineering, commissioning and qualification, to demonstrate that all of these required controls have been properly implemented and verified (including function where applicable, such as alarms on operating parameters);
iv appropriate control and oversight of change once the controls have been verified.

  1. The scope and extent of qualification and re qualification should be determined based on the principles of impact assessment and risk management.
    Qualification should be executed by trained personnel. Training records should be maintained.
    Where appropriate, new premises, systems, utilities and equipment should be subjected to all stages of qualification. This includes the preparation of user requirements specification (URS), design qualification (DQ), installation qualification (IQ), operational qualification (OQ) and performance qualification (PQ).
    Where it is decided that not all stages of qualification are required, justification should be provided.
    Qualification should be done in accordance with predetermined and approved qualification protocols. The protocol should specify the prerequisites and test details, including acceptance criteria.
    The results of the qualification should be recorded and reflected in qualification reports.

2. Normally, qualification stages should be sequential (e.g. operational qualification should follow after the successful completion of installation qualification). In some cases, different stages of qualification may be executed concurrently. This should be justified and documented in the validation master plan (or qualification protocol).
3. Equipment should be released for routine use only once there is documented evidence that the qualification has been successful.
4. Certain stages of the qualification may be done by a supplier or a third party, subject to the conditions and responsibilities as defined in writing and agreed between the parties. The contract giver remains responsible to ensure that the qualification is done in accordance with the principles of good manufacturing practices.
5. The relevant documentation associated with qualification, including standard operating procedures, specifications and acceptance criteria, certificates and manuals, should be available.
6. Utilities and equipment should be maintained in a qualified state and should be periodically reviewed for the need for requalification and Re qualification should be considered when changes are made.

User requirements specification

URS documentation should be prepared for, but not limited to, utilities and equipment, as appropriate.

URS should be used at later stages in qualification, to verify that the purchased and supplied utility or equipment is in accordance with the user’s needs.

Design Qualification

DQ should demonstrate that the system, as designed, is appropriate for its intended use as defined in the URS.

A suitable supplier should be selected and approved for the relevant utility or equipment.

Factory acceptance test and site acceptance test

Where a utility or equipment is assembled, or partially assembled at a site other than that of the purchaser or end-user, testing and verification may be done, based on principles of quality risk management, to ensure that it is appropriate, as described in the URS, and ready for dispatch.
The checks and tests conducted during the factory acceptance test (FAT) should be recorded.
The acceptability of the assembly and overall status of the utility or equipment should be described in a conclusion of the report for the FAT, prior to shipment.
Tests, based on principles of quality risk management, may be performed to verify the acceptability of the utility or equipment when it is received at the end-user. This is a site acceptance test (SAT).
The results of the tests should be evaluated and the outcome of the acceptability of the utility or equipment should be recorded in the conclusion section of the report for the SAT.

Installation qualification

Utilities and equipment should be correctly installed, in an appropriate location.
There should be documented evidence of the installation. This should be in accordance with the IQ protocol, which contains all the relevant details.
IQ should include identification and installation verification of relevant components identified (e.g. services, controls and gauges).

Identified measuring, control and indicating devices, should be calibrated on site, unless otherwise appropriately justified. The calibration should be traceable to national or international standards. Traceable certificates should be available.
Deviations and non-conformances, including those from URS, DQ and acceptance criteria specified and observed during installation, should be recorded, investigated and corrected or justified.

The outcome of the IQ should be recorded in the conclusion of the report, before OQ is started.

Operational qualification

Requirements and procedures for operation (or use), calibration, maintenance and cleaning should be prepared before OQ and approved prior to PQ.
Utilities and equipment should operate correctly and their operation should be verified in accordance with an OQ protocol. OQ normally follows IQ but, depending on the complexity of the utility or equipment, it may be performed as a combined installation/operation qualification (IOQ). This should be justified and documented in the validation master plan (or qualification protocol).

OQ should include, but is not limited to, the following:
Tests that have been developed from the knowledge of processes, systems and equipment, to ensure the utility or equipment is operating as designed;
tests over the operating limits.

Training of operators for the utilities and equipment should be provided and training records maintained.
Calibration, cleaning, maintenance, training and related tests and results should be verified to be acceptable.
Deviations and non-conformances observed should be recorded, investigated and corrected or justified.
The results for the verification of operation should be documented in the OQ report.
The outcome of the OQ should be recorded in the conclusion of the report,normally before PQ is started.

Performance qualification

PQ should normally follow the successful completion of IQ and OQ. In some cases, it may be appropriate to perform PQ in conjunction with OQ or process validation. This should be justified and documented in the validation master plan (or qualification protocol).

PQ should include, but is not limited to, the following:
tests using production materials, qualified substitutes or simulated products proven to have equivalent behaviour under operating conditions, with batch sizes where appropriate;
tests covering the intended operating range.

Utilities and equipment should consistently perform in accordance with their design specifications and URS. The performance should be verified in accordance with a PQ protocol.
There should be records for the PQ (e.g. a PQ report), to indicate the satisfactory performance over a predefined period of time. Manufacturers should justify the period over which PQ is done.

Periodic review and Re qualification

1. Utilities and equipment should be maintained in a qualified state throughout the life-cycle of the utility or equipment.
2. Utilities and equipment should be reviewed periodically, to confirm that they remain in a qualified state or to determine the need for re qualification.
3. Where the need for re qualification is identified, this should be performed.
4. Principles of risk management should be applied in the review and re qualification and the possible impact of small changes over a period of time should further be considered (such as, through change control).
5. Principles of risk management may include factors such as calibration, verification, maintenance data and other information.
6. The qualification status and periodic re qualification due dates should be documented, for example, in a qualification matrix, schedule or plan.
7. In case a utility or equipment in use is identified that has not been subjected to qualification, a qualification protocol should be prepared where elements of URS, design specifications, operation and performance are verified for acceptability. The outcome of this qualification should be recorded in a report.

Working and Principle of Tablet Coating Machine

What are the Main Parts of Tablet Coating Machine

Automated Control System

This is the part of the tablet Coating machine that automatically controls its various functions.

Such functions include operating/running of the machine, process data display, speed, pressure, and temperature.

This helps in ensuring the efficiency of the machine.

Electric Motors

Electric motors facilitate various operations of the tablet Coating Machine.

These functions include blowing air, mixing the tablets, and creating negative pressure.

Electric motors are present in different sections of the tablet coating machine.

They include a coating drum, hot air equipment, peristalsis pump and the air exhaust section.

Touch Screen Operating Panel

This is that part of the machine that an operator can observe, input various control and monitor its operations which has a user-friendly interface for easy operation.

Guide Plate

The function of a guide plate in a tablet coating machine is to allow for the smooth tumbling of the tablets. This is essential when blowing hot air through the tablets during the drying process.

It is also important in the mixing process of the tablets.

Peristaltic Pump

Stepper Motor Coating Machine Supporting Dispensing Peristaltic Pump|peristaltic  pump|pump pumpstepper motor peristaltic pump - AliExpress

A peristaltic pump offers constant pressure to the Tablet coating machine, thereby eliminating the need for return pipes. It also aids in the stabilization of the atoms during the spraying process.

Spraying System

The spraying system consists of the nozzle, tank, and a pump.

Its functions include the atomization stability, cleaning, and maintenance of the spraying gun and storing the tablet coating solution.

It also minimizes spraying gun plug-up and ensures even and efficient atomization.

Pan Cooling Surface

The pan cooling Surface consists of an Automatic Load cell System that helps in regulating the volume of the spraying solution.

It also consists of the electronic pulse valve, a Discharging device, an Exhaust dust collector, an air heating unit, and an air distribution device.

Other parts include; a Magnetic stirrer, air pipes, and fittings, and a flexible drum filter holder.

Coating Preparation Tank

This is where the preparation of the coating solution takes place.

How does Tablet Coating Machine Work

The working of a tablet Coating machine involves the selection of suitable materials.

This is dependent on the kind of tablets that you are using and the desired final coating process.

There are criteria that you can use to select the best coating materials.

The next step is the tablet spinning which involves putting the tablets in a drum and rotating it in an orbital way.

It is a continuous process where the streamlined plates control most of the operations.

As the drum spins, a nozzle sprays a coating solution to the tablets.

It is an automatic process that an operator controls using the controlling system.

This helps in ensuring there are accuracy and an even spray of the tablets.

Also, the angled baffles present in the drum turn the tables sideways facilitating even spraying of the tablets, while the spaying and rotation continue, the machine pumps hot air into the drum which results in the rapid coating of the solution.

The machine allows for the self-regulation of the hot air temperature that flows within it and the reason for this excess temperature can affect the chemical composition of the tablets.

The machine also regulates the pressure within the drum in line with that of the outside environment.

After all the tablets have a uniform coating, the spinning and spraying stop, the tablets then proceed to the drying section.

Here, air flows over the tablets and drying them.

There is regulation as to the volume of air that flows to ensure there is no reaction with the tablets. Once this is over, your tablets are ready for packaging.

Automatic Capsule Filling machine working Principle

Introduction :

Pharmaceutical processing involves a number of operations and capsule filling is one such important part of the process. This can be done either manually or by means of an automated capsule filling machine.

The capsule before sent for packing needs to be properly processed and filled with the help of a capsule Filling machine. The capsules are rectified, caps and bodies are separated, active pharmaceutical ingredients (API) is filled, wasted capsules are rejected, capsules are locked in place, ejaculated and then cleaned and all this done with the help of a capsule filler. An automated filling machine will take care of the entire filling process itself. If you run a large scale production firm, then using automated capsule filler is a must. These machines boost production and improve the efficiency of the production process. The complete functioning of an automated capsule filling machine is detailed below.

Loading of Raw Materials

The first thing that you have to confirm is the condition of the machine which should be proper.

After that, we will load the empty capsules and the filling material into respective product hoppers. we will power on the machine by pressing the start button for the machine to commence operation. we should also key in the major operation parameters at the PLC control system to guide the operations of the machine.

Capsule rectification

The capsules produced in a factory mostly have their caps and bodies joined and they need to be rectified before the filling process begins. For rectification, the capsules are fed into the capsule delivery plate with multiple circular channels inside to hold the capsules. The capsules are then allowed to fall on a horizontal fork that acts on the center of the capsule and then the vertical fork adjusts the direction of them. Capsule rectification is now complete and it is followed by separating the caps and bodies.

Separating capsule caps and bodies

After rectification, the capsule tray is moved to the capsule filling station and the caps and bodies of the capsule are separated by means of a vacuum divider. Once the capsule separation is done, the cap and the body are transferred to their respective stations.

Medication filling

The body of the capsule is transferred to the filling station where the active ingredients are filled in the capsule. It can be done by a number of different methods.

Tamping filling

The powder here is compacted with the help of a tamping punch. The powders are transferred from one tamping punch to next to achieve a smooth finish.

Intermittent dosator filling

In this method, the empty dosage tubes are inserted in a dosage hopper and the dosage punch inside the tube crushes the ingredients into a fine powder.

Dosage cylinder filling

In this method, two dosage pistons under the hopper control the filling of ingredients. This type of filling is especially suitable for filling particle-sized ingredients.

Vacuum filling

This method directly pulls ingredients inside the dosage tube by means of a vacuum pull. Compressed air is then used to blow the powdered content into the capsule body.

Waste capsule rejection

When the filling process is carried out, sometimes some of the capsule bodies do not separate from the capsule caps and as such are wasted products. There are pins inside the machine that pulls such capsules out of the mold and blows them into a collecting bag. The capsule caps and bodies are then both transferred to the next station for locking.

Locking capsule

The two trays containing the capsule bodies and caps rotate in sync in the locking station and the baffle plate located above the capsule tray and the pin is located under the tray moves as well to lock the two parts of the capsule in place.

Capsule ejection

Once the capsule is locked in place an ejection device, which is quite similar to the capsule rejection device, ejects the locked capsules out of the capsule tray and sends them to the outlet.


Once all the capsules are ejected, the tray moves back to the first station, i.e the capsule rectification table. The tray is then cleaned for any powdered remains or waste capsule bits. Compressed air is used to clean the try and the debris is collected at the dust collecting system below.  Mechanical polishing can also be done to keep the filling machine shiny and remove unwanted adhesives and ingredients from its surface.

Inspection of Capsule

Inspection procedure  for Capsule :

After line clearance, transfer the filled capsule in SS tray or on the inspection table layered with HDPE polythene bag and spread the capsules on inspection table.
Capsule should be visually checked for various defects (Dented, telescopic, Poor printing or no printing on capsules, Poor locking Quality, Improper polishing, Double caps Empty capsule etc) & Rejected capsules should be kept in Polythene bag containing online rejection label as per SOP of “Procedure for Status Labelling” .
Collect the good capsules in HDPE container lined with double polythene bags and weigh  and label it properly as per Batch Manufacturing record
Summary of rejection quantity for various defect of capsule shall be recorded as per provision given in Batch Manufacturing record
Some Picture of various defect of capsule given below for clarity regarding distinguish the different types defect.
Pictures of various Defect of Capsule

Autoclave Working Principles

An autoclave is a sterilization device that is widely used in in hospitals, Pharmaceutical industries and laboratories. Sterilization is critical within the pharmaceutical and medical industries.

How do Autoclave works :

An autoclave is a device that works on the principle of moist heat sterilisation, wherein saturated steam is generated under pressure in order to kill microorganisms such as bacteria, viruses, and even heat-resistant endospores from various types of instruments. This is done by heating the instruments within the device to temperatures surpassing the boiling point of water.

This process is also embodied by gas laws, which basically states that the higher the pressure is within the device, the higher the temperature increases. In other words, pressure and temperature are directly proportional to each other.

It is also important to note that it is the temperature that kills the microorganisms, not pressure. Rather, higher pressures are capable of increasing the boiling point of water, which thus increases the temperature of sterilization. High pressure also helps heat to rapidly spread within the material.

Autoclaves typically yield a temperature of about 121 degrees Celsius, taking about 15-20 minutes to complete the sterilization process. However, autoclave cycles may be adjusted accordingly by the working technician. 

Autoclaves are grounded on three factors, namely: pressure, temperature, and time. These three factors all work together to create saturated steam, within a particular time frame, that can kill all signs of microbial life, whether they are in vegetative or spore form.

What is The Operating Procedure of Autoclave :

1). Check if there are previous instruments, Glass, stainless steel, cultures etc contained within the chamber.

2). Put water in the chamber and make sure it is the right amount.

3). Place the instruments, Glass, stainless steel, cultures etc inside the chamber which are required to be sterilized.

4). Close the lid and tighten the screws then switch on the electric heater.

5). Adjust the safety valves to maintain the required pressure level within the chamber.

6). Once the water within the chamber begins to boil, the air-water mixture can escape through the discharge tube in order to displace all the air inside. Complete displacement is evident when no more water bubbles come out from the pipe.

7). Close the drainage pipe and let the steam reach the desired level.

8). Once the pressure level has been reached, blow the whistle to remove all the excess pressure within the chamber.

9). Let the autoclave run for the set time period after the whistle.

10). Switch off the electric heater and let the autoclave cool until the pressure within the chamber has lowered down to the atmospheric pressure.

11). Open the discharge pipe to allow air from outside the autoclave to enter. 

12). Open the lid and remove the instruments from the chamber.

The Stages of Autoclave Sterilization :

The sterilization process includes different phases

  1. Purge Phase : During this phase steam displaces air within the autoclave chamber and both temperature and pressure begin to increase
  2. Sterilization Phase : The exhaust remains closed, allowing the temperature and press to rapidly rise to the desired values. It is during this phase that autoclaves harsh conditions destroy bacteria, spores and other pathogens.
  3. Exhaust Phase : Pressure is released from chamber, but temperature remain high. Operator or microbiologist should take care when removing hot contents from autoclave.

Autoclave Compatible and Incompatible Materials

Compatible Materials Incompatible Materials
Biological cultures and stocksMaterials containing solvents, volatile or corrosive, or flammable chemicals
Culture dishes and related materialsMaterial contaminated with chemotherapeutic agents or cytotoxic drugs
Contaminated solid items (i.e. pipette tips, gloves, Petri dishes, etc.)Material containing Bleach*
Discarded live (including attenuated) viruses/vaccinesCarcinogens or mutagens (i.e. ethidium bromide)
Polypropylene (PP) and polycarbonate (PC) plasticsPhenol and Trizol
Borosilicate glassPolystyrene (PS), polyethylene (PE), and high-density polyethylene (HDPE) plastics
Stainless steelHoushold glassware

Equipment Usage Logbook-Procedure and Format

What is Equipment usage logbook :

The purpose of this Document is for Recording the usage, cleaning and maintenance activity of Equipment in a chronological order, with done by, checked and reviewed by signature.

Separate Equipment usage log shall be issued for each process Equipment and Issued Equipment usage log book shall be used for execution.

Equipment Logbook shall be the person who has done or perform the activity and shall be checked by another person for correctness.

  •  All equipment user logs shall be under the control of quality assurance department.
  • The equipment user log shall contain the following details.
  • Equipment information
  • The first page of all equipment log shall contain the equipment information  i.e., equipment name, equipment number, model and month.
  • Equipment user log issued from quality assurance department on request of production.
  • Equipment user log format.
  •  Equipment user log shall contain the details of user log (Annexure-1)
  • Quality assurance department shall issue the equipment user log for equipment on rising of requisition slips fore equipment user log duly approved by  In-charge /executive.
  • The respective section In-charge shall verify the equipment user log.
  • The executive Quality Assurance department shall review all the log for every 15 days. In case of any discrepancy, the same should be brought to the notice of the respective department In-charge for corrective action.
  •  The completed user log shall be returned to QA department.
  •  Document controller shall store the completed log.

Entries in user log :

  • All the entries shall be made with black ballpoint pen.
  • If any column is not applicable, enter NA in the respective column.
  • Time shall be entered as hours round the clock. For ex: 12 AM shall be entered as 00.00 hour and 1:00 PM shall be entered as  13:00hour.
  • Any events related to the instrument shall be entered in remarks  column otherwise enter “Nil”.
  • The respective department operator /executive shall fill all the  columns in the user log before starting the procedure / analysis  except end time and remarks column. End time and remarks  column shall be filled after the completion of activity.

Correction of wrong entries:

For any error during entry, the following process followed and In case, any wrong entry occurs, strike it out with a single line.

Clearly write the correct entry near the wrong entry.

Sign and put the date on which the correction was made.

 If an entire line has to be deleted, strike it out with a single line (horizontal/vertical).

 Write a note explaining the reason for deletion with sign and date.  

The section-in-charge shall verify and counter sign on the same.

Annex – 1 Equipment Usage Logbook